Biochemical and functional alterations of central GABA receptors during chronic estradiol treatment

Hamon, Michel; Goetz, Christopher G.; Euvrard, C.; Pasqualini, Catherine; Dafniet, M. Le; Kerdelhué, B.; François, Clément; Peillon, F

doi:10.1016/0006-8993(83)90172-5

Cited by 60 publications

(17 citation statements)

References 33 publications

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“…Estradiol and progestagens may modify levels of other transmitters or hormones which in turn affect the GABAa re ceptor [11]. As a consequence, the presence or absence of different hormone-sensitive regulatory factors in specific brain regions could contribute to the site specificity of hormonal effects.…”

Section: Discussionmentioning

confidence: 99%

Regulation of High-Affinity GABAa Receptors in Specific Brain Regions by Ovarian Hormones

Schumacher¹,

Coirini²,

McEwen³

1989

Neuroendocrinology

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The regulation of ³H-muscimol binding to high-affinity GABAa receptors by estradiol (E) and by progesterone (P) was studied within discrete brain regions using in vitro quantitative autoradiography. Treatment of ovariectomized and adrenalectomized female rats with E resulted in a decrease of muscimol binding only in specific estrogen-sensitive brain regions like the ventromedial nuclei (VMN) of the hypothalamus, the arcuate nucleus (ARC), the medial amygdala and the midbrain central grey (MCG). When administered alone, P had no effect. However, in estrogen-primed females, P increased muscimol binding in both VMN and MCG to levels seen in control animals. Thus, E and P exert opposite effects on the the GABAa receptor within these two nuclei. As both hormones facilitate female reproductive behavior as well as the release of luteinizing hormone, present results suggest that E and P affect muscimol binding by different mechanisms.

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Section: Discussionmentioning

confidence: 99%

Regulation of High-Affinity GABAa Receptors in Specific Brain Regions by Ovarian Hormones

Schumacher¹,

Coirini²,

McEwen³

1989

Neuroendocrinology

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“…Unlike GABA which is present in neuronal and extra-neuronal h u e , its synthetic enzyme GAD is only found in GABAergic nene terminals (1,21,22) and so changes in its concentration reflect changes in GABA itself (I). Steroids reduce GAD concentration in the ventral tegmentum, septum and substantia nigra (6,34,35) and daily injections of OB, that would inhibit LH release and stimulate prolactin release, induce changes in GAD activity in a number of hypothalamic regions; some reports have shown that mstrogen can increase GAD activity in the posterior hypothalamus and ME (26, 27), but it is suggested that this is an indirect effect exerted via raised prolactin levels (25,36,38). Others have shown that OB treatment reduced GAD activity in the VMN, ARC and anterior hypothalamus, but not in the POA (24), however two further papers found no change in any of the hypothalamic areas investigated (9,23).…”

Section: Ospmentioning

confidence: 99%

Ovarian Steroid Regulation of Glutamic Acid Decarboxylase Gene Expression in Individual Hypothalamic Nuclei

Leigh

Carter

Horton

et al. 1990

J Neuroendocrinology

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The possibility that steroids exert their effects on luteinizing hormone (LH) and prolactin release and female sexual behaviour via altering 7-arninobutyric acid (GABA) synthesis within the hypothalamus was investigated. Ovariectomized rats were treated with e$ther oil, 5 pg oestradiol benzoate (OB) or 5 pg OB plus 0.5 mg progesterone (P) 48 h later; autopsy was carried out 54 h after the OB injection. At this time, both steroid treatments stimulated prolactin release and lordotic activity. OB alone exerted a negative feedback effect on LH release while OB plus P stimulated an LH surge.The brains of the rats in these three treatment groups were microdissected and glutamic acid decarboxylase messenger ribonucleic acid (GAD mRNA) was estimated in specific hypothalamic areas obtained from individual brains; these areas included the preoptic area (POA), ventromedial nucleus (VMN), anterior medial portion of the zona incerta (ZI) and the arcuatehedian eminence area (ARC/ME). GAD mRNA concentrations were assessed by the slot-blotting technique and expressed as a ratio of GAD mRNA: b-actin mRNA.Both steroid treatments significantly reduced GAD mRNA in the ARCIME and ZI and OB plus P also reduced the concentration in the POA, while OB alone had no effect in this area. Neither treatment affected GAD mRNA in the VMN. These results indicate that when steroids stimulate LH and prolactin release and female sexual behaviour, they reduce GABA activity probably by reducing GABA synthesis in the POA, ZI and ARCIME. This suggests that GABA normally has an inhibitory influence on these parameters. G4BA synthesis does not however, appear to be involved in the negative feedback effects of steroids on LH release as measured 54 h after OB treatment.;,-,iminobutyric acid (GABA) is widely distributed in the hypothalmius with its highest concentrations in the preoptic area (POA) aiid ventromedial nucleus (VMN) (1 -3). GABA-containing neurons possess steroid receptors (4, 5 ) and it has becn suggested that sri:roids might exert some of their CNS effects via GABAergic s! stems (6-9). These effects include the control of luteinizing hormone (LH) and prolactin release and sexual behaviour. Rep x t s in the literature indicate that GABA can influence sexual bchaviour in females (10, 11) and has a dual effect on the release of I €1 and prolactin (12, 13). The results show that GABA is inhibitory to LH release in the POA and anterior medial portion o!' the zona incerta (ZI) (14-17). The site of it's stimulatory effect is not really known, although some data indicate that it may be in the medial basdl hypothalamus (12,18,19). Within the hypothalaIlIus GABA stimulates prolactin release, but it is inhibitory at the level of the pituitary (12)(13)(14)20). There are many reports investigating the inter-relationship of the gonadal steroids and GABA, in particular noting the effect of oestrogen and progesterone (P) on GABA activity in specific brain areas. Since GABA is present in both neuronal and glial tissue (1, 21) changes in its concentra...

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“…In the HPOA region both an elevated con centration of T and E receptors [30] as well as a high aromatase activity [22] have been found in the male quail brain. A steroid-dependent regulation of BZ receptor Bmax has been demonstrated in rodent forebrain areas [ 10,13]; moreover, a specific T effect responsible for the de creased number of GABA binding sites has recently been encountered in the hypothalamic area of the male rat brain [16]. The localization of a gonadal steroid effect on BZ receptors in the HPOA suggests that a steroid-BZ in teraction might be involved in the regulation of sociosexual behavior in the male quail.…”

Section: Discussionmentioning

confidence: 99%

Distribution of Benzodiazepine Binding Sites in the Brain of the Male Japanese Quail and Its Correlation to a Hormonal Control: Quantitative Autoradiography Study

Canonaco

Tavolaro²,

Cerra³

et al. 1992

Neuroendocrinology

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Quantitative receptor autoradiography was used to study the neuroanatomical distribution and effects of gonadal hormones on [³H] flunitrazepam binding in the male Japanese quail brain. In gonadally intact quail brains, [³H] flunitrazepam displayed a heterogeneous distribution, with elevated levels in the posterior brain regions such as the stratum griseum et fibrosum superficiale and stratum griseum centrale of the optic tectum. Lower values were observed in the anteriorly located brain sites such as the nucleus septalis (lateralis et medialis), the cortex dorsolateralis and the nucleus lateralis hypothalami. Castration affected [³H] flunitrazepam binding levels in brain areas known to contain gonadal steroid receptors as well as in some areas which were devoid of gonadal steroid receptors. Castration in fact, elevated [³H] flunitrazepam binding in the nucleus preopticus anterior and reduced binding levels in archistriatum dorsalis et ventralis and in the nucleus intercollicularis; all of these areas are known to have gonadal steroid receptors. In two regions which do not contain such receptors, namely the hyperstriatum ventrale and the cerebellum pars granularis, castration increased [³H] flunitrazepam binding. In order to determine whether the gonadal steroid effect is due to changes either in the number of binding sites (B_max) and or affinity binding state (KD), saturation binding studies were carried out in some of the areas described above in brains of quail which were castrated or castrated and given replacement therapy with testosterone or estradiol for 2 weeks. In keeping with the suppressive effect of the gonads inferred from the castration results described above, testosterone and estradiol decreased the B_max of [³H] flunitrazepam binding in the hypothalamus preoptic area, while in hyperstriatum ventrale only estradiol produced a significant decrease of the B_max. We then tested for the effects of GAB A on [³H] flunitrazepam binding to the receptors and found that GABA intensified the depressive activity of gonadal steroid replacement therapy in the hyperstriatum ventrale and in the hypothalamus-preoptic area as shown respectively by the approximate 45 and 40% greater decrease of B_max. However when the GABA effect on [³H] flunitrazepam binding in the presence of GABA was expressed as ratio, only the hyperstriatum ventrale revealed a significantly enhanced potentiation effect following castration, while a significant suppression of this potentiation effect was obtained by both T and E replacement therapy. These results suggest that a GABA-benzodiazepine receptor interaction might be involved in the regulation of some hormone-mediated cerebral functions in the male quail such as neuroendocrine and sociosexual behavior.

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Biochemical and functional alterations of central GABA receptors during chronic estradiol treatment

Cited by 60 publications

References 33 publications

Regulation of High-Affinity GABAa Receptors in Specific Brain Regions by Ovarian Hormones

Regulation of High-Affinity GABAa Receptors in Specific Brain Regions by Ovarian Hormones

Ovarian Steroid Regulation of Glutamic Acid Decarboxylase Gene Expression in Individual Hypothalamic Nuclei

Distribution of Benzodiazepine Binding Sites in the Brain of the Male Japanese Quail and Its Correlation to a Hormonal Control: Quantitative Autoradiography Study

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